Prognostic value of perioperative changes in serum primary metabolites in patients after major surgery under general anesthesia: an exploratory secondary analysis of the TAPIR trial.

Abstract

Purpose: Major surgery under general anesthesia substantially alters physiologic homeostasis. Nevertheless, the intricate effects on the metabolome are poorly studied. Metabolic fingerprints may allow the identification of patients at risk for unfavourable outcomes.

Methods: We conducted a secondary, exploratory, targeted metabolomic analysis of 177 high-risk patients undergoing major abdominal surgery under general anesthesia enrolled in the Targeting preoperatively Assessed Personal cardiac Index in major abdominal suRgery patients (TAPIR) randomized controlled trial. We analyzed primary serum metabolites using liquid chromatography coupled with triple quadrupole mass spectrometry before surgery (on preoperative day 0) and on postoperative day 3 (POD3). Our primary aim was to investigate postoperative alterations in primary serum metabolites. Secondary objectives included analyses in different subgroups, including patients with postoperative complications (composite of complication, delirium, acute kidney injury, and infection) up to day 30. We applied regression analyses and calculated false discovery rate-adjusted P values to address multiplicity.

Results: Of the 37 metabolites analyzed, 20 were different on POD3 after comparison with before surgery (lower: 4-hydroxyproline, alanine, asparagine, citrulline, cystine, dimethylglycine, glutamine, glutamic acid, glycine, guanosine, histidine, niacinamide, serine, uric acid, and xanthine; higher: isoleucine, leucine, methionine, methionine sulfoxide, pyruvic acid; adjusted P values < 0.05). We found no statistically significant preoperative differences between patients with and without postoperative complications (all adjusted P values ≥ 0.05). Postoperatively, patients with (vs without) delirium within thirty days after surgery (n = 13/177) showed lower levels of alanine, asparagine, citrulline, cystine, glutamine, glutamic acid, serine, threonine, and tyrosine after adjusting for preoperative metabolite levels.

Conclusion: Major abdominal surgery under general anesthesia was associated with complex changes in primary metabolites. We identified alterations in certain metabolites that were associated with postoperative delirium. Future research may establish metabolic patterns allowing the identification of patients at risk for unfavourable postoperative outcomes.